Expression profiling in spondyloarthropathy synovial biopsies highlights changes in expression of inflammatory genes in conjunction with tissue remodelling genes

Thomas, Gethin P., Duan, Ran, Pettit, Allison R., Weedon,Helen, Kaur, Simranpreet, Smith, Malcolm and Brown, Matthew A. (2013) Expression profiling in spondyloarthropathy synovial biopsies highlights changes in expression of inflammatory genes in conjunction with tissue remodelling genes. BMC Musculoskeletal Disorders, 14 . doi:10.1186/1471-2474-14-354


Author Thomas, Gethin P.
Duan, Ran
Pettit, Allison R.
Weedon,Helen
Kaur, Simranpreet
Smith, Malcolm
Brown, Matthew A.
Title Expression profiling in spondyloarthropathy synovial biopsies highlights changes in expression of inflammatory genes in conjunction with tissue remodelling genes
Journal name BMC Musculoskeletal Disorders   Check publisher's open access policy
ISSN 1471-2474
Publication date 2013-12-15
Sub-type Article (original research)
DOI 10.1186/1471-2474-14-354
Open Access Status DOI
Volume 14
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central Ltd.
Language eng
Subject 2732 Orthopedics and Sports Medicine
2745 Rheumatology
Abstract Background: In the spondyloarthropathies, the underlying molecular and cellular pathways driving disease are poorly understood. By undertaking a study in knee synovial biopsies from spondyloarthropathy (SpA) and ankylosing spondylitis (AS) patients we aimed to elucidate dysregulated genes and pathways. Methods. RNA was extracted from six SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: Four hundred and sixteen differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, B-cell associated, matrix catabolic, and metabolic pathways. Altered «myogene» profiling was also identified. The inflammatory mediator, MMP3, was strongly upregulated (5-fold) in AS/SpA samples and the Wnt pathway inhibitors DKK3 (2.7-fold) and Kremen1 (1.5-fold) were downregulated. Conclusions: Altered expression profiling in SpA and AS samples demonstrates that disease pathogenesis is associated with both systemic inflammation as well as local tissue alterations that may underlie tissue damaging modelling and remodelling outcomes. This supports the hypothesis that initial systemic inflammation in spondyloarthropathies transfers to and persists in the local joint environment, and might subsequently mediate changes in genes directly involved in the destructive tissue remodelling.
Keyword Ankylosing spondylitis
Gene expression
Inflammation
Microarrays
Spondyloarthritis
Synovial membrane
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
 
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